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The Vps35 D620N Mutation Linked to Parkinson's Disease Disrupts the Cargo Sorting Function of Retromer
Author(s) -
Follett Jordan,
Norwood Suzanne J.,
Hamilton Nicholas A.,
Mohan Megha,
Kovtun Oleksiy,
Tay Stephanie,
Zhe Yang,
Wood Stephen A.,
Mellick George D.,
Silburn Peter A.,
Collins Brett M.,
Bugarcic Andrea,
Teasdale Rohan D.
Publication year - 2014
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12136
Subject(s) - retromer , endosome , vacuolar protein sorting , microbiology and biotechnology , biology , transport protein , mutant , sorting nexin , protein targeting , biochemistry , membrane protein , intracellular , gene , membrane
A genetic mutation in the Vps35 subunit of retromer has recently been linked to late onset Parkinson's disease. We observed that the distribution and maturation of Vps35 D620N positive endosomes are altered. While Vps35 D620N containing retromer still binds CI‐M6PR , its trafficking is perturbed as shown by secretion of its ligand cathepsin D. As cathepsin D is involved in processing of α‐synuclein, a well‐established causative agent of Parkinson's disease, its altered trafficking may therefore represent the underlying cause of disease.